Carbon Dioxide → HCID 69347016, compound

HRID 855310Notes

Reaction equation

HRID 855310 reaction equation
[Li]CCCC.CCCCCC.[F:12][C:13]1[CH:21]=[C:20]2[C:16]([CH:17]=[CH:18][NH:19]2)=[CH:15][C:14]=1[C:22]([F:25])([F:24])[F:23].CC(C)([O-])C.[K+].[C:32](=[O:34])=[O:33]>C1COCC1.O>[F:12][C:13]1[C:21]([C:32]([OH:34])=[O:33])=[C:20]2[C:16]([CH:17]=[CH:18][NH:19]2)=[CH:15][C:14]=1[C:22]([F:25])([F:23])[F:24]

Participants

8

Reactant 5

HCID 280Carbon DioxideHCID 8058HexaneHCID 23665647Potassium tert-butoxideHCID 69365533HCID 69365533, compoundHCID 178418339Butyllithium

Product 1

HCID 69347016HCID 69347016, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A 1.6 molar solution of n-BuLi in hexane (1.38 ml, 2.2 mmol) was diluted with 3 ml THF and cooled to −78° C. Then, a solution of 203 mg of 6-fluoro-5-trifluoromethyl-1H-indole (1 mmol) in 1 ml THF was added dropwise, keeping the internal temperature below −70° C. After 5 min a solution of 269 mg potassium tert-butoxide (2.4 mmol) in 1 ml THF was added, again keeping the internal temperature below −70° C. The reaction mixture was then stirred for 2 h. Then dry ice was added and the mixture was allowed to warm to 10° C. Water was added and the phases were separated. The aqueous phase was washed twice with ether, then acidified with 1 N HCl solution and extracted several times with DCM. The combined DCM extracts were dried with magnesium sulfate, filtered and the solvent was evaporated. The remaining residue was triturated with pentane. Final filtration yielded 105 mg (42%) of 6-fluoro-5-trifluoromethyl-1H-indole-7-carboxylic acid as an off-white solid. 1H-NMR (DMSO-d6, 300 MHz): δ 6.63 (m, 1H), 7.43 (t, J=3 Hz, 1H), 8.15 (d, J=7 Hz, 1H), 11.49 (br s, 1H), 13.70 (br s, 1H).

Workup

  1. customthe internal temperature below −70° C
  2. customthe internal temperature below −70° C
  3. temperatureto warm to 10° C
  4. customthe phases were separated
  5. washThe aqueous phase was washed twice with ether
  6. extractionextracted several times with DCM
  7. dry with materialThe combined DCM extracts were dried with magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe remaining residue was triturated with pentane
  11. filtrationFinal filtration

Sources & evidence

ORD record
ord-6ce67befd9834119b286a79dd0988b70
Source dataset
uspto-grants-2007_08
Patent number
US07259183B2

Reaction notes

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